Human immune response phenotypes, including specific IgE and IgG antibody and lymphocyte responses to ultrapure pollen allergens, and total basal serum IgE level, are of uncertain genetic determination. These phenotypes will be explored for consistency, familial aggregation and genetic determination in people selected for allergy and their families. If these traits are indeed found to be Mendelian, then linkage analysis and genetic mapping, including possible mapping of Ir loci in the major histocompatibility complex, will be done. Populations to be studied include a series of allergic volunteers; a set of family-based Amish rural dwellers; and a new group of allergic persons identified from an occupational survey (with suitable comparison groups). Particular features of this project will be: (1) the use of ultrapure allergens for all immunologic analysis; (2) serological typing of non-HL-A antigens expressed on lymphocytes; (3) careful study and characterization of the mixed lymphocyte response; (4) use of Galtonian as well as Mendelian genetic models in statistical analysis; (5) development of new techniques for linkage analysis of closely-linked loci in human populations. We anticipate that many new findings concerning the genetics of allergy and immune response in man will emerge from this project which will be of direct relevance in our understanding of human disease.